Eradicating Gastric Cancer With Iridium

Researchers in China have developed a novel drug that could help diagnose and treat gastric cancer.

AsianScientist (Mar. 9, 2020) – Using iridium—the second most dense metal—researchers in China have developed a drug that specifically targets gastric cancer cells. Their findings are published in the journal Angewandte Chemie.

One in 12 cancer deaths worldwide is due to gastric cancer, making it the third deadliest cancer in the world after lung and colorectal cancer. Current treatments for colorectal cancer include surgery and chemotherapy, but each comes with its own side effects.

In the present study, researchers led by Dr. Chen Yu at Sun Yat-Sen University and Professor Chao Hui at the Hunan University of Science and Technology have found a way to simultaneously diagnose and target colorectal tumors using a drug called FerriIridium. The initially weakly-active precursor, based on an iridium-containing compound, is selectively activated only after reaching the interior of a tumor cell.

FerriIridium gains entry into cancer cells when the cells fold in small regions of their membranes and pinch them off—a process known as endocytosis. The endocytosed drug then fuses with lysosomes, an acidic structure that contains trivalent iron ions and enzymes. In gastric cancer cells, the concentration of trivalent iron ions within the lysosomes is significantly elevated.

The researchers demonstrated that FerriIridium exerts its anticancer effect by triggering the production of highly reactive hydroxyl radicals. The radicals destroy the lysosomes, releasing their contents inside the cancer cells, leading to further damage to cellular constituents. Additionally, the splitting of FerriIridium drastically increases both the phosphorescence and the toxicity of the iridium complex. This phosphorescence can be used to diagnose the tumor.

Most importantly, the toxic iridium complex is absorbed by mitochondria, the ‘power plants’ of the cell, collapsing their membrane potential and triggering programmed cell death. In experiments involving cancer cells grown in petri-dishes and mice, the researchers showed that FerriIridium had potent anticancer properties.

The article can be found at: Kuang et al. (2020) FerriIridium: A Lysosome‐Targeting Iron(III)‐Activated Iridium(III) Prodrug for Chemotherapy in Gastric Cancer Cells.


Source: Wiley; Photo: Shutterstock.
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